Deferoxamine iron chelation increases delta-aminolevulinic acid induced protoporphyrin IX in xenograft glioma model.

Exogenous administration of delta-aminolevulinic acid (delta-ALA) leads to selective accumulation of protoporphyrin IX (PpIX) in brain tumors, and has shown promising results in increasing extent of resection in fluorescence-guided resection (FGR) of brain tumors. However, this approach still suffers from heterogeneous staining and so some tumor margins may go undetected because of this variation in PpIX production. The aim of this study was to test the hypothesis that iron chelation therapy could increase the level of fluorescence in malignant glioma tumors. Mice implanted with xenograft U251-GFP glioma tumor cells were given a 200 mg kg(-1) dose of deferoxamine (DFO), once a day for 3 days prior to delta-ALA administration. The PpIX fluorescence observed in the tumor regions was 1.9 times the background in animal group without DFO, and 2.9 times the background on average, in the DFO pre-treated group. A 50% increase in PpIX fluorescence contrast in the DFO group was observed relative to the control group (t-test P-value = 0.0020). These results indicate that iron chelation therapy could significantly increase delta-ALA-induced PpIX fluorescence in malignant gliomas, pointing to a potential role of iron chelation therapy for more effective FGR of brain tumors.

Tissue permittivity: a monitor for progressive tissue fibrosis as observed in bystander tissues following experimental high dose rate irradiation.

Fibrosis is a pathological condition resulting from radiation injury which often limits the prescription of higher (or boost) doses of radiation, risking inadequate tumor control in patients. Recent studies have documented reduction in fibrotic lesions after administration of pentoxyfilline and tocopherol combinations to breast cancer patients receiving adjuvant radiation therapy. Despite the promise of these findings, no techniques or markers are available which can be used to identify the onset or progression of fibrosis in such patients at stages early enough to allow maximum benefit from these types of pharmacological agents. Relative permittivity of skeletal muscle has been investigated in an animal model utilizing high dose rate radiation both at the treatment site as well as on the contralateral site, and was found to be directly related to the formation and progression of fibrotic lesions. A cubic increase in the quantified fibrotic fraction of the tissue (2.7%-13.9% over 11 w post irradiation) was reflected in a linear increase in the tissue's relative permittivity (epsilon(r) = 6.3-8.8 over 11 w post irradiation). These findings mandate further investigation of the relationship between tissue's relative permittivity and subcellular injury leading to fibrosis using electrical impedance spectroscopy (EIS).

Broadband frequency-domain near-infrared spectral tomography using a mode-locked Ti:sapphire laser.

Frequency-domain near-infrared (NIR) diffuse spectral tomography with a mode-locked Ti:sapphire laser is presented, providing tunable multiwavelength quantitative spectroscopy with maximal power for thick tissue imaging. The system was developed to show that intrinsically high stability can be achieved with many wavelengths in the NIR range, using a mode-locked signal of 80 MHz with heterodyned lock-in detection. The effect of cumulative noise from multiple wavelengths of data on the reconstruction process was studied, and it was shown that inclusion of more wavelengths can reduce skew in the noise distribution. This normalization of the data variance then minimizes errors in estimation of chromophore concentrations. Simulations and tissue phantom experiments were used to quantify this improvement in image accuracy for recovery of tissue hemoglobin and oxygen saturation.

Microwave thermal imaging of scanned focused ultrasound heating: phantom results.

We are developing a microwave tomographic imaging system capable of monitoring thermal distributions based on the temperature dependence of the recovered dielectric properties. The system has been coupled to a high intensity focused ultrasound (HIFU) therapy device which can be mechanically steered under computer control to generate arbitrarily shaped heating zones. Their integration takes advantage of the focusing capability of ultrasound for the therapy delivery and the isolation of the microwave imaging signal from the power deposition source to allow simultaneous treatment monitoring. We present several sets of phantom experiments involving different types of heating patterns that demonstrate the quality of both the spatial and temporal thermal imaging performance. This combined approach is adaptable to multiple anatomical sites and may have the potential to be developed into a viable alternative to current clinical temperature monitoring devices for HIFU, such magnetic resonance (MR) imaging.